Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Early Breast Cancer Neoplasms, Breast ErbB2+
Interventions:	Drug: Lapatinib Biological: Trastuzumab Drug: Paclitaxel

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Lapatinib 1500 mg	Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenously (IV) for an additional 12 weeks
Trastuzumab 2 mg/kg	Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg	Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks

Participant Flow: Overall Study

	Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
STARTED	154	149	152
COMPLETED	101	137	92
NOT COMPLETED	53	12	60
Adverse Event	29	2	32
Lost to Follow-up	0	0	1
Protocol Violation	0	1	1
Withdrawal by Subject	5	0	1
Recurrence of Disease	3	4	1
Participant Withdrawal from Drug	0	0	3
Missing	1	1	1
Other: Reason Not Specified	15	4	20

Baseline Characteristics

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Reporting Groups

	Description
Lapatinib 1500 mg	Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenously (IV) for an additional 12 weeks
Trastuzumab 2 mg/kg	Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg	Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks

Baseline Measures

	Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg	Total
Number of Participants [units: participants]	154	149	152	455
Age [units: Years] Median ( Full Range )	50.0 ( 28 to 79 )	49.0 ( 23 to 77 )	50.0 ( 25 to 80 )	50.0 ( 23 to 80 )
Gender [units: Participants]
Female	154	149	152	455
Male	0	0	0	0
Race/Ethnicity, Customized [units: participants]
American Indian or Alaska Native	13	14	15	42
Asian - Central/South	7	5	5	17
Asian - East	30	28	31	89
Asian - South East	0	0	2	2
Black or African American/African Heritage	0	4	4	8
White - Arabic/North African Heritage	6	5	3	14
White - Caucasian European Heritage	97	93	92	282
Missing	1	0	0	1
Number of participants with tumor cells of the indicated histologic grade ^[1] [units: participants]
Well differentiated	2	5	5	12
Moderately differentiated	56	53	63	172
Poorly differentiated	73	68	64	205
Differentiation cannot be assessed	22	23	20	65
Missing	1	0	0	1
Number of participants with lymph nodes (LNs) of the indicated clinical N stage ^[2] [units: participants]
N0	34	41	48	123
N1	95	85	80	260
N2 (including N2a and N2b)	19	13	15	47
N3 (including N3a, N3b, and N3c)	6	7	6	19
Nx	0	3	3	6
Number of participants with the indicated IHC results ^[3] [units: participants]
Not applicable	60	53	61	174
Equivocal: Score of 2+	9	5	8	22
Positive: Score of 3+	81	89	76	246
Negative: Score of 0-1+	0	1	3	4
Non interpretable	4	1	4	9
Number of participants with the indicated FISH results ^[4] [units: participants]
Not applicable	38	42	41	121
Amplified	115	105	109	329
Not amplified	1	2	1	4
Not interpretable	0	0	1	1

[1]	Histologic grade, also called differentiation, refers to how much the tumor cells resemble normal cells of the same tissue type.
[2]	Clinical N stage is an evaluation/staging of LN status through physical examination. N0, no regional LN metastasis; N1, metastasis to movable ipsilateral axillary LNs (IALNs); N2a, metastasis in IALNs fixed to one another (matted) or the other structures; N2b, metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary LN metastasis; N3a, metastasis in ipsilateral infraclavicular LNs; N3b, metastasis in ipsilateral internal mammary LNs fixed and axillary LN; N3c, metastasis in ipsilateral subclavicar LNs; Nx, not assessed.
[3]	An Immunohistochemistry (IHC) test gives a score of 0 to 3+, which indicates the amount of Human Epidermal Growth Factor (HER2) receptor proteins on the cancer cells in the sample tissue. A positive score (3+) indicates that HER2 receptor protein is present, a negative score (0-1+) indicates that no HER2 receptor protein is present, and an equivocal score (2+) indicates uncertainty and a result that is open for interpretation. Equivocal results require additional testing. “Not applicable” refers to the number of participants who did not have IHC testing done.
[4]	The Fluorescent In Situ Hybridization (FISH) assay was used to determine the overexpression and/or amplification of HER2 in the invasive component of the primary tumor. Amplified indicates that the cell is overexpressing copies of the HER2 gene. Not amplified indicates that there is no overexpression of copies of the HER2 gene. “Not applicable” refers to the number of participants who did not have the FISH assay performed.

Outcome Measures

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1. Primary:

Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery [ Time Frame: Weeks 20 to 22 ]

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2. Secondary:

Number of Participants With Overall Response at Week 6 [ Time Frame: Week 6 ]

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3. Secondary:

Number of Participants With Overall Response at the Time of Surgery [ Time Frame: Time of surgery (Weeks 20 to 22) ]

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4. Secondary:

Number of Participants With Negative Lymph Nodes at the Time of Surgery [ Time Frame: Time of surgery (Weeks 20 to 22) ]

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5. Secondary:

Number of Participants With Actual Indicated Surgery [ Time Frame: At surgery (Weeks 20 to 22) ]

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6. Secondary:

Estimate of Treatment Contrast for Change From Baseline in Tumor Size at Week 6 and at Surgery [ Time Frame: Week 6 and surgery (Weeks 20 to 22) ]

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7. Secondary:

Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab [ Time Frame: Week 6 ]

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8. Secondary:

Overall Survival [ Time Frame: Following surgery, every 12 months until Year 10 ]

Results not yet posted. Anticipated Posting Date: 01/2020 Safety Issue: No

9. Secondary:

Disease-free Survival (DFS) [ Time Frame: Following surgery, every 12 months until Year 10 ]

Results not yet posted. Anticipated Posting Date: 08/2013 Safety Issue: No

10. Secondary:

Number of Participants With Metabolic Response of Complete Response (mCR), Partial Response (mPR), or Stable Disease (mSD) as Determined by Positron Emission Tomography/Computed Tomography (PET/CT) [ Time Frame: Baseline, Week 2, and Week 6 ]

Results not yet posted. Anticipated Posting Date: 12/2011 Safety Issue: No

11. Secondary:

Number of Participants With the Indicated Biomarker Expression [ Time Frame: Baseline, Week 2, and at surgery (Weeks 20 to 22) ]

Results not yet posted. Anticipated Posting Date: 01/2013 Safety Issue: No

12. Secondary:

Number of Circulating Tumor Cells (CTC) in the Bloodstream [ Time Frame: Baseline, Week 2 of neo-adjuvant phase (Weeks 1-34), at surgery (Weeks 20 to 22), Week 10 of adjuvant phase, 6 months after completion of adjuvant treatment, and at recurrence ]

Results not yet posted. Anticipated Posting Date: 01/2013 Safety Issue: No

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00553358 History of Changes
Other Study ID Numbers:	EGF106903
Study First Received:	November 1, 2007
Results First Received:	May 26, 2011
Last Updated:	February 2, 2012
Health Authority:	Spain: Ministry of Health; Lithuania: State Medicine Control Agency - Ministry of Health; Germany: Federal Institute for Drugs and Medical Devices; United States: Food and Drug Administration; United Kingdom: Medicines and Healthcare Products Regulatory Agency